Fondaparinux Sodium

(BAN, USAN, rINN)
Synonyms: Fondaparin Sodium; Fondaparinuks Sodyum; Fondaparinuuksinatrium; Fondaparinux sódico; Fondaparinux Sodique; Fondaparinuxnatrium; Fondaparinuxum Natricum; Fondaparinuxum Natrium; Org-31540; SR-90107A.
Cyrillic synonym: Фондапаринукс Натрия.

💊 Chemical information

CAS — 114870-03-0.
ATC — B01AX05.
ATC Vet — QB01AX05.

💊 Adverse Effects

As for Heparin.

💊 Treatment of Adverse Effects

If bleeding occurs fondaparinux should be stopped and appropriate therapy given. Unlike heparin, there is no specific antidote for fondaparinux (but see below).

Overdosage.

Activated eptacog alfa (recombinant factor VIIa) given 2 hours after an injection of fondaparinux was found1 in healthy subjects to normalise coagulation times and thrombin generation for up to 6 hours, suggesting that it may be useful to treat bleeding complications, or if acute surgery is needed.
1. Bijsterveld NR, et al. Ability of recombinant factor VIIa to reverse the anticoagulant effect of the pentasaccharide fondaparinux in healthy volunteers. Circulation 2002; 106: 2550–54.

💊 Precautions

As for Heparin. Fondaparinux should not be given to patients who have developed thrombocytopenia with heparin and who have a positive in-vitro platelet aggregation test (that is, cross-reactivity) in the presence of fondaparinux itself. Fondaparinux is contra-indicated in severe renal impairment, and special care is required in patients with body-weight below 50 kg.

💊 Interactions

As for Heparin.

💊 Pharmacokinetics

After subcutaneous injection fondaparinux sodium is rapidly and completely absorbed, with bioavailability of 100%. It is extensively bound in plasma, predominantly to antithrombin III. It is excreted in the urine, with 64 to 77% of a dose excreted unchanged. The elimination half-life is between 17 and 21 hours, but is prolonged in patients with renal impairment, in the elderly, and in those weighing less than 50 kg.
1. Donat F, et al. The pharmacokinetics of fondaparinux sodium in healthy volunteers. Clin Pharmacokinet 2002; 41 (suppl 2): 1–9
2. Paolucci F, et al. Fondaparinux sodium mechanism of action: identification of specific binding to purified and human plasmaderived proteins. Clin Pharmacokinet 2002; 41 (suppl 2): 11–18.

Pregnancy.

Although an in vitro study1 reported that fondaparinux does not cross the placenta, a small study2 in pregnant women who had received fondaparinux found that anti-factor Xa activity was elevated in umbilical cord blood, suggesting that a small amount of placental transfer had taken place.
1. Lagrange F, et al. Fondaparinux sodium does not cross the placental barrier: study using the in-vitro human dually perfused cotyledon model. Clin Pharmacokinet 2002; 41 (suppl 2): 47–9
2. Dempfle C-EH. Minor transplacental passage of fondaparinux in vivo. N Engl J Med 2004; 350: 1914–15.

💊 Uses and Administration

Fondaparinux is a synthetic pentasaccharide that acts as a selective inhibitor of activated factor X. It is used as the sodium salt as an anticoagulant in the management of venous thromboembolism, unstable angina, and acute myocardial infarction. It has also been used in patients with heparininduced thrombocytopenia. For prophylaxis of venous thromboembolism in abdominal and orthopaedic surgery, fondaparinux sodium is given by subcutaneous injection in a dose of 2.5 mg once daily, starting 6 to 8 hours after surgery and continued for at least 5 to 9 days, or up to 32 days in hip fracture. For prophylaxis in high-risk medical patients, the same dose is given once daily for 6 to 14 days. In the initial treatment of venous thromboembolism, fondaparinux sodium is given by subcutaneous injection once daily at a dose of 5 mg for patients weighing less than 50 kg, 7.5 mg for weight 50 to 100 kg, and 10mg for weight over 100kg. Treatment is usually continued for 5 to 9 days, and at least until oral anticoagulation is established. Fondaparinux is also used in unstable angina and acute ST-elevation myocardial infarction, but is only indicated in patients for whom urgent percutaneous coronary intervention is not planned. It is given in a dose of 2.5 mg subcutaneously once daily for up to 8 days, with the first dose given intravenously in acute ST-elevation myocardial infarction. Heparin should be given at the time of the procedure if percutaneous coronary intervention is performed and fondaparinux should be restarted when clinically appropriate. Doses of fondaparinux may need to be reduced in patients with renal impairment (see below).
1. Keam SJ, Goa KL. Fondaparinux sodium. Drugs 2002; 62: 1673–85
2. Tran AH, Lee G. Fondaparinux for prevention of venous thromboembolism in major orthopedic surgery. Ann Pharmacother 2003; 37: 1632–43
3. The Matisse Investigators. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med 2003; 349: 1695–1702
4. Reynolds NA, et al. Fondaparinux sodium: a review of its use in the prevention of venous thromboembolism following major orthopaedic surgery. Drugs 2004; 64: 1575–96
5. Büller HR, et al. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial. Ann Intern Med 2004; 140: 867–73
6. The OASIS-6 Trial Group. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA 2006; 295: 1519–30
7. Cohen AT, et al. ARTEMIS Investigators. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. Abridged version: BMJ 2006; 332: 325–9. Full version: http://www.bmj.com/cgi/reprint/332/7537/325 (accessed 14/05/08
8. Yusuf S, et al. Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med 2006; 354: 1464–76
9. Efird LE, Kockler DR. Fondaparinux for thromboembolic treatment and prophylaxis of heparin-induced thrombocytopenia. Ann Pharmacother 2006; 40: 1383–7.

Administration in renal impairment.

Fondaparinux is eliminated renally and should be used with caution in patients with renal impairment. US licensed product information contraindicates its use in patients with creatinine clearance (CC) below 30 mL/minute, and advises caution in those with CC between 30 and 50 mL/minute. UK licensed product information contra-indicates its use in patients with creatinine clearance (CC) below 20 mL/minute; for patients with CC between 20 and 50 mL/minute a subcutaneous dose of 1.5 mg once daily is recommended for prophylaxis of venous thromboembolism, but no dosage alteration is required for unstable angina or myocardial infarction.

💊 Preparations

Proprietary Preparations

Austral.: Arixtra; Belg.: Arixtra; Braz.: Arixtra; Canad.: Arixtra; Cz.: Arixtra; Denm.: Arixtra; Fin.: Arixtra; Fr.: Arixtra; Ger.: Arixtra; Gr.: Arixtra; Hong Kong: Arixtra†; Indon.: Arixtra; Ital.: Arixtra; Malaysia: Arixtra; Mex.: Arixtra; Neth.: Arixtra; Quixidar; Norw.: Arixtra; NZ: Arixtra†; Pol.: Arixtra; Port.: Arixtra; Quixidar†; Rus.: Arixtra (Арикстра); Singapore: Arixtra; Spain: Arixtra; Swed.: Arixtra; Switz.: Arixtra; Thai.: Arixtra; UK: Arixtra; USA: Arixtra.
Published March 12, 2019.